NANOTECHNOLOGY: A TOOLKIT FOR CELL BEHAVIOR - 3D Bioprinting and Nanotechnology in Tissue Engineering and Regenerative Medicine - page 5

Carbon nanotubes can also be leveraged to bolster very weak materials and render them usable
for tissue engineering applications that otherwise would be less than ideal. Electrospinning (to be
described in Section 3.1), a common nano scaffold fabrication technique, can be used to gener-
ate tissue-engineered cartilage constructs ( Holmes et al . , 2012 ). However, the Young's modulus
of the resulting scaffolds is often much lower than autologous tissue. To combat this, Holmes
et al . used H 2 purified MWCNTs ( Figure 1.2 B) to create an electrospun nanocomposite scaffold
with a Young's modulus more similar to cartilage, and, with the addition of a polylysine coating,
improved chondrogenic differentiation of MSCs significantly when compared to controls ( Holmes
et al . , 2013 ).
1.2.1.2 Carbon Nanofibers
Similar to CNTs, carbon nanofibers consist of graphene sheets rolled into 3D structures with
cone or cylindrical-shaped morphology. A carbon nanofiber can be defined as “sp2-based lin-
ear filaments with diameter of 100 nm that are characterized by flexibility and their aspect ratio
(above 100)” ( Kim et al . , 2013 ) as seen in Figure 1.1 . Carbon nanofibers are usually manufactured
through vapor deposition with or without a metal catalyst ( Endo, 1988 ), or less commonly, using a
mechanical spinning process ( Li et al . , 2004 ). Carbon nanofibers have been used throughout tissue
engineering to improve mechanical properties and cellular activity, for multiple tissue regenera-
tion applications.
For bone regeneration, Elias et al . reported that osteoblast proliferation and long-term functions (i.e.
synthesis of alkaline phosphatase and deposition of extracellular calcium up to 21 days) can be sig-
nificantly improved on 60 nm diameter carbon nanofibers without a pyrolytic outer layer and 100 nm
diameter carbon nanofibers with a pyrolytic outer layer compared to conventional larger carbon fibers
( Elias et al . , 2002 ). Since it is well known that surface properties (i.e. surface area, surface roughness,
and number of surface defects) of implant materials may have important influences on cell functions
(including adhesion, proliferation, differentiation, and mineralization) ( Zhang et al . , 2008c ; Webster
et al . , 2000 ), enhanced long term osteoblast functions on carbon nanofibers have been attributed to the
special nanometer surface topography of carbon nanofibers which mimics the dimension of inorganic
crystalline hydroxyapatite and collagen in natural bone.
Carbon nanofibers are also attractive in neural tissue engineering due to their excellent structural
and electrical properties, and from a practical perspective are relatively inexpensive. One approach
to utilize carbon nanofibers is to attach or grow them on a conductive polymer to create an array of
fibers, and then seed cells onto the construct ( Nguyen-Vu et al . , 2007 ). This not only allows for im-
proved electrical conductivity of the material, but the neural cells also demonstrated good electrical
contact with the nanofibers. Leveraging these observed advantages, carbon nanofibers were injected
into stroke-damaged rat brain defects. The rats that were injected with neural stem cells in tandem with
carbon nanofibers formed significantly less glial scar tissue when compared to positive and negative
controls, indicating a more successful neural repair ( Lee et al . , 2006 ).
1.2.1.3 Graphene
Graphene is the simplest nanomaterial form of carbon, and functions as a base unit for all other car-
bon nanomaterials. It consists of one monolayer of carbon atoms bonded in sp 2 hybridization orbit-
als. Sought after as a nanomaterial constituent of composite materials, graphene has a high elastic
modulus, high electrical conductivity, and the potential to increase nanotexturization of surfaces. These